title: Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis.
  
  
  METHODS
  We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied.
  
  
  RESULTS
  Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples.
  
  
  CONCLUSIONS
  We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.
authors.affiliation: *Unit of Pathological Anatomy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; †Department of Surgical, Medical, Molecular Pathology, and Critical Area, Division of Pathological Anatomy, University of Pisa, Pisa, Italy; ‡Unit of Thoracic Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; and §Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Thoracic Surgery, University of Pisa, Pisa, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Alì
authors.forename: Nicla
authors.initials: N
authors.lastname: Borrelli
authors.forename: Giannini
authors.initials: G
authors.lastname: Riccardo
authors.forename: Agnese
authors.initials: A
authors.lastname: Proietti
authors.forename: Serena
authors.initials: S
authors.lastname: Pelliccioni
authors.forename: Cristina
authors.initials: C
authors.lastname: Niccoli
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D039422:Integrin alpha3; D012333:RNA, Messenger; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14